Evidence map›Paper›PMID 26880577›Full record

ArticleThe Journal of experimental medicine2016

Functional screen identifies regulators of murine hematopoietic stem cell repopulation.

Per Holmfeldt, Miguel Ganuza, Himangi Marathe, Bing He, Trent Hall, Guolian Kang, Joseph Moen, Jennifer Pardieck, Angelica C Saulsberry, Alba Cico and 5 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 98 citations in OpenAlex.

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  17. Cells · 2022
    Article
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Per HolmfeldtDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Miguel GanuzaDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Himangi MaratheDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Bing HeInterdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242.
Trent HallDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Guolian KangDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105.
Joseph MoenDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105.
Jennifer PardieckDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Angelica C SaulsberryDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Alba CicoDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Ludovic GautDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Daniel McGoldrickDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.
David FinkelsteinDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Kai TanDepartment of Internal Medicine, University of Iowa, Iowa City, IA 52242.
Shannon McKinney-FreemanDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105 shannon.mckinney-freeman@stjude.org.
St. Jude Children's Research Hospital · USUniversity of Iowa · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GERARD PAUL ZAMBETTI · 1985 to 2026
$166.9M
Defining Nfix's role as a novel key regulator of hematopoietic stem cellsR01DK104028 · NIDDK · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MCKINNEY-FREEMAN, SHANNON L · 2016 to 2020
$2.0M
EPIGENETIC REGULATION OF STEM CELL FATE CHOICER01HG006130 · NHGRI · UNIVERSITY OF IOWA · PI TAN, KAI · 2012 to 2016
$1.7M
A TOOLKIT FOR IDENTIFYING CAUSAL VARIANTS IN TRANSCRIPTIONAL ENHANCERSR01GM104369 · NIGMS · UNIVERSITY OF IOWA · PI TAN, KAI · 2014 to 2017
$1.2M
Characterization of embryonic stem cell-derived hematopoietic stem cellsK01DK080846 · NIDDK · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MCKINNEY-FREEMAN, SHANNON L · 2008 to 2012
$771k
Epigenetic landscapes of embryonic lymphoid progenitors and HSCsR21HD081054 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI SPECK, NANCY, TAN, KAI · 2015 to 2016
$441k
NCI NIH HHS P30 CA021765NHGRI NIH HHS HG006130NHGRI NIH HHS R01 HG006130NICHD NIH HHS R21 HD081054NIDDK NIH HHS K01 DK080846NIDDK NIH HHS K01DK080846NIDDK NIH HHS R01 DK104028NIGMS NIH HHS R01 GM104369
6 · The paper itself

Abstract

Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA-transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251. Knockdown of each of these genes yielded a loss of function, except in the cases of Armcx1 and Gprasp2, whose loss enhanced hematopoietic stem cell (HSC) repopulation. The discovery of multiple genes regulating vesicular trafficking, cell surface receptor turnover, and secretion of extracellular matrix components suggests active cross talk between HSCs and the niche and that HSCs may actively condition the niche to promote engraftment. We validated that Foxa3 is required for HSC repopulating activity, as Foxa3(-/-) HSC fails to repopulate ablated hosts efficiently, implicating for the first time Foxa genes as regulators of HSPCs. We further show that Foxa3 likely regulates the HSC response to hematologic stress. Each gene discovered here offers a window into the novel processes that regulate stable HSPC engraftment into an ablated host.

Indexed as

Genetic Association StudiesAmino Acid MotifsAnimalsCell ProliferationCytoprotectionEnhancer Elements, GeneticGenetic TestingHematopoiesisHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHepatocyte Nuclear Factor 3-gammaMice, Inbred C57BLProtein BindingReproducibility of ResultsSignal TransductionStress, PhysiologicalFoxa3 protein, mouseHepatocyte Nuclear Factor 3-gamma

Identifiers

PMID26880577
PMCPMC4813668
OpenAlexW2294592209

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.